Human epidemiology and experimental animal data have provided the statistical association and
biological information necessary to propose that
aflatoxins are risk factors for human
liver cancer. As
liver cancer causes at least 200,000 deaths per year, prevention measures must be developed to ameliorate this nearly always fatal disease. Preventive strategies will be facilitated by the identification of individuals at high risk. It is the goal of the molecular dosimetry field to provide facile and accurate
biomarkers to identify people at high risk for
carcinogen exposure and consequent adverse health effects. We have developed methods to defect the major
aflatoxin DNA adduct,
aflatoxin N7-guanine (AFB-N7-guanine), in urine, examined the dose-response characteristics in people living in China and The Gambia, and have found an excellent association of this
biomarker with exposure. In addition to exposure studies in people, our laboratories have monitored AFB-N7-guanine excretion in the urine of rats whose risk for developing
cancer has been modulated with dietary chemoprotective agents such that independent groups of animals receiving the same dosage of
aflatoxin B1 were at either high or low risk for
tumorigenesis. The production of DNA damage by
aflatoxins is not the exclusive mechanism for
liver cancer. Many other factors, including hepatitis B virus, cell proliferation, and nutritional status, can exert strong modification effects in human disease. Thus, molecular epidemiological investigations that examine only one
biomarker may greatly underestimate or overestimate the risk for an individual.(ABSTRACT TRUNCATED AT 250 WORDS)